Background and aim of the study: diabetes wasproposed to be an inflam­matory disease.  Growing evidence has pointed to a correlation between various proinflammatory cytokines, insulin resistance (IR) and type 2 diabetes (T2DM). Materials and Methods: This study was carried out on one hundred Albino rats, distributed into four groups. Group I: control group, Group II: diabetic rats with no treatment, Group III:  diabetic rats treated with Glipenclamid and Group IV: diabetic rats treated with Diclofenac sodium. Blood samples were taken and the following biochemical parameters were done: fasting blood glucose (FBG), serum insulin, aspartate transaminase (AST), Alanine transaminase (ALT), serum Alkaline Phosphatase (ALP), serum protein, serum albumin, serum triglyceride (TGs), serum cholesterol level (TC), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Tumor Necrosis Factor (TNF-α) and C-Reactive Protein (CRP). HOMA IR and HOMA B were calculated. Liver samples from all rats were obtained and stained with Hematoxylin and Eosin, Masson's trichrome and Periodic acid–Schiff (PAS) for histological examination. Results: Declofenac caused significant lowering in FBG, lipid profile, TNF-α level, CRP, increased insulin secretion with improved IR and beta cell function compared to the diabetic group. There was a positive correlation between HOMA-IR and CRP; HOMA-IR and serum TNF-α. Liver of diabetic rats showed periportal fibrosis, vacuolated cytoplasm and nuclei and glycogen deposition. These changes improved markedly in Glibenclamide treated groups while liver of Declofenac treated group revealed parenchymal cell necrosis, sinusoidal dilatation with some pyknotic nuclei and marked glycogen deposition. Conclusions: inflammatory pathways may play an important part in IR of T2DM. Therefore, antinflammatory drugs may have a role in diabetes therapy through improving IR because of its insulin-sensitiz­ing and anti-inflammatory properties.