Background: Diabetes mellitus is a heterogeneous group of syndromes characterized by elevation of fasting blood glucose that is caused by a relative or absolute deficiency in insulin. Diabetes is the leading cause of amputation and adult blindness and a major cause of nerve damage, renal failure, heart attacks, and stroke. Exogenous insulin is essential for the management of Diabetes mellitus type 1 and has an adjunct role in the management of type 2 diabetes mellitus in which oral hypoglycemic medicines display the leading management role. Pain, Lipodystrophy at the injection site, Nerve damage, Thermolabile, and microbial contamination during injection are the principal adverse effects of insulin administered via IV or SC routes. Objective: Production and screening of sublingual recombinant human insulin drug delivery system. Methods: Type of study: Screening experimental study. Micronization process like Jet or bead milling was utilized to make micronized particles of recombinant human insulin less than 50 microns which resulted in more drug solubility and better absorption through biological and physiological membranes of the human body. This resulted in better bioavailability of the drug. In our study, micronized Insulin sublingual tablets were designed which were able to avoid the hepatic first-pass effect and gastrointestinal degradation. The sublingual tablets were prepared by direct compression technique utilizing different concentrations of starch 1500 and microcrystalline cellulose. DSC and FTIR spectroscopy were utilized in the drug and the polymer compatibility studies. Evaluation of preformulation properties of active principal ingredient (API) was performed. As well postcompressional parameters such as wetting time, disintegration time, in vivo bio-availability, in vitro drug release, and water absorption ratio study of the optimized formulation were assessed. Results: The disintegration time of the optimized formulation was up to 45 seconds. The in vitro release of insulin from optimized sublingual tablets was found to be up to 15 minutes. The percentage relative bioavailability of insulin from optimized sublingual tablets was 81%. The pre-compression parameters were within an acceptable range of pharmacopeia specifications. No possible interactions were noticed between the drug and the polymer via FTIR spectroscopy and DSC study. The sublingual tablet of insulin was tested on animal models, evaluated in human clinical trials phases 1/2, and compared with standard regular soluble insulin injection formulations for efficacy. The sublingual formulation of insulin showed high bioavailability and efficacy. Conclusion: The sublingual tablets of recombinant human insulin helped to overcome the disadvantages of subcutaneous injections of insulin.