This study was designed to investigate the possible protective role of kefir beverage on kidney structure biologically, histochemical and some biochemical parameters such as cholesterol level, MCP-1, and resistin in high-fat diet-fed streptozotocin-diabetic rats. 60 rats were divided into two experiments by six groups: experiment Ⅰ included 3 non-diabetic ones and experiment ⅠⅠ included three STZ- induced diabetes groups. The groups were fed as follows: group 1 received a standard diet and served as control. Group 2 was fed on a standard diet and kefir (0.7 ml/animal/day by gavage). Group 3 received a high-fat diet and kefir (0.7 ml/animal/day by gavage). The diabetic males of groups A, B, and C were fed on the high-fat diet. Group B received besides kefir (0.7 ml/animal/day by gavage), while group C was injected additionally with insulin (0.76 UI/200 mg BW/day). After 5 weeks, animals of all groups were sacrificed. From the cell biological, histochemical, and histopathological conceptions, both kefir and insulin have various effects on cellular activities and different chemical materials contents, such as DNA, RNA, total protein, collagen, polysaccharides, and lipoproteins, in the examined normal and diabetic renal tubule cells of the male rats. Overall, it seems like kefir beverage may, to some extent, completely repair the diabetic pathological side effects such as kidney dysfunction regarding keeping the kidney tissue structurally almost normal with some changes in the histochemical components investigated, also there was an improvement in cholesterol level with a beneficial effect on lowering inflammatory markers. Finally, kefir highly reduces the collagen formation in the renal cells that prevent renal nephron from its function and we propose probably kefir treats kidney failure as a side effect of diabetes, by a mechanism that is opposite to the proposed mechanism, for the formation of this kidney failure induced by diabetes, via us in the present work.