Background: Diabetic myopathy is a common complication of diabetes mellitus (DM), yet experimental studies concentrated on insulin deficiency and motor neuropathy as the cause. C-peptide deficiency has recently been implicated in the pathogenesis of diabetic neuropathy. However, its effects on the contractile properties of skeletal muscles need investigation. Objective: Testing the gastrocnemius muscle response to electric stimulation in normal and type II diabetic adult male albino rats with and without treatment by C-peptide or nitric oxide modulators and correlating it with the metabolic error.  Material and methods: Thirty six adult male albino rats of a local strain and average weight (160-170g) were equally divided into the following groups: 1- Control group (C): normal non diabetic rats kept on normal pellet diet (NPD) without any treatment, Diabetic groups; Type II diabetes was induced by high fat diet (HFD), followed after 2 weeks by a single intraperitoneal injection of low dose streptozotocin (STZ) to induce partial pancreatic β-cell damage.  One week after STZ injection, diabetes was verified by high serum glucose level (≥ 200 mg/dl), and diabetic rats were further classified into the following groups according to subsequent treatment; 2-Diabetic control (no further treatment), 3-Diabetic+C-peptide, 4-Diabetic+ N^G-L-Arginine Methyl Ester (L-NAME); a nitric oxide synthase (NOS) inhibitor, 5-Diabetic+C-peptide+L-NAME, and 6-Diabetic+L-arginine; the substrate of NOS. Treatment continued for 4 weeks, during which rats were maintained on normal or HFD according to group. Under urethane anesthesia, the right gastrocnemius was exposed, subjected to direct electric stimulation with maximal low frequency stimulation. The peak force and the time till 50% fatigue (1/2 the peak force) were determined. The left gastrocnemius served as resting muscle. The experiment was then terminated by stopping stimulation and, immediately, rats were decapitated, blood samples were collected, and both gastrocnemius muscles were excised from origin to insertion and the liver was taken. Tissue and serum samples were subjected to biochemical analysis. Results: HFD and STZ injection induced the metabolic error of type II diabetes in rats with diabetic myopathy picture characterized by significant lowering of peak muscle force, muscle weight, muscle and liver glycogen with a significant shortening of the time till 50% fatigue. The generalized metabolic error was manifested by hyperglycemia, hypoinsulinemia, increased insulin resistance indicated by a higher homeostatic model of insulin resistance (HOMA-IR), and dyslipidemiawith higher atherogenic index. Oxidative stress was manifested by a significantly high malodialdehyde (MDA) and nitric oxide was significantly lowered. These errors were corrected with C-peptide treatment, but its beneficial effects were partially antagonized by L-NAME combination.  L-arginine treatment partially corrected, while L-NAME treatment alone worsened the error. Conclusion: Metabolic and functional deterioration occurred in the gastrocnemius muscles of type II diabetic rat model as a cause and effect of the generalized metabolic error present.  C-peptide treatment acted as insulin mimetic and corrected to a significant level both errors. This effect was partially mediated by endogenous NO production. C-peptide could be a future substitution treatment for diabetic myopathy or chronic fatigue of the metabolic syndrome.