Abstract: The aim of the research was to study the potential of various grades of hydroxypropylmethyl cellulose (HPMC) in enhancing oral bioavailability of insulin. Enteric coated HPMC-insulin granules (HPMC-insulin granules), enteric coated control granules (control granules or placebo) of only HPMC and control (peroral) solution of zinc insulin in glycerine IP were tested in vivo in rats. An assay value of 99.6±1.6% of HPMC-insulin granules confirmed the minimal insulin degradation during granulation/coating process. In vivo studies showed maximum blood glucose lowering with K100LV-insulin granules corresponding to a relative pharmacological efficacy of 1.399±0.138% and absolute pharmacological efficacy of 0.537±0.059%. In contrast, neither control granules nor control (peroral) solution showed a comparable effect. The multiple comparison post-hoc test, LSD (p-level of 0.05), showed a significant difference of K100LV, E50LV, E5LV, E4M-insulin granules from control (untreated) and of only K100LV, E50LV-insulin granules from control (peroral) solution on grades vs. controls basis. On grades vs. grades basis, the potential of HPMCs in lowering of blood glucose levels was finalized as K100LV>E50LV>E5LV≅E4M> K4M>K100M. It is concluded that low viscosity grades of HPMC are efficient in enhancing oral insulin absorption as compared to very low and high viscosity grades. However, viscosity appears to mask effect of substitution ratio on insulin absorption.