Introduction: Diabetic nephropathy (DN) is one of most prevalent diabetic complication. It remains unclear whether the anti-inflammatory Hydroxytyrosol (HT) has beneficial effects on biogenesis of diabetic renal changes. So, we aimed to find out the relationship between inflammation, apoptosis, oxidative stress and the progression of DN. Also, try to assess the possible effects of HT on diabetic renal tissue. Materials and Methods: Rats were divided into: non-diabetic rats (group I) and rats with induced type II diabetes that were subdivided into: group II non-treated DM, group III treated with HT, group IV treated with glyclazide and group V treated with combined treatment. Treatments were supplied for eight weeks. Results: Administration of HT alone or with GLY significantly lowered blood glucose levels and ameliorated kidney hypertrophy index together with improving renal dysfunction parameters including creatinine in serum and urine, blood urea nitrogen, serum and urinary albumin, together with the tissue oxidative markers and inflammatory cytokines activities compared to diabetic group. These effects of HT were also reflected on histologic evaluation and Nrf2- Keap1 system expression. Conclusion: This study discovers the renoprotective effect of HT in diabetic rats. Hence, this study recommended an addition of antioxidants like HT to the management of diabetes.