AbstractBackground: Metformin hydrochloride is a very potentanti-diabetic drug that has become the drug of choice for thetreatment of type 2 diabetes.Aim of Study: This work aims todemonstrate the effect of metformin hydrochloride administration and its withdrawal on the histological structure and function of the kidney of adult male albino rats.Material and Methods: Sixty adult male albino rats wereused in this work. They were divided equally into six groups; I- First control group (Group C1), II- Second control group (Group C2), III- Third control group (Group C3), IV- Treated group (Group T), V- First recovery group (Group R1) and VI-Second recovery group (Group R2). Each adult male albino rat of groups C1 and T was given 0.55ml of distilled water and 0.55ml of distilled water (contained 27.45mg metformin hydrochloride) respectively for four weeks. Each adult male albino rat of groups C2 and R1 was given 0.55ml of distilled water and 0.55ml of distilled water (contained 27.45mg metformin hydrochloride) respectively for four weeks, then, left for two weeks without treatment. Each adult male albino rat of groups C3 and R2 was given 0.55ml of distilled water and 0.55ml of distilled water (contained 27.45mg metformin hydrochloride) respectively for four weeks, then, left for four weeks without treatment. The treatments were given once/day orally. The specimens were collected at three time intervals; at the end of the 4th week for groups C1 & T, at the end of the 6th week for groups C2 & R1 and at the end of the 8th week for groups C3 & R2. The blood samples were collected for measuring urea and creatinine. The kidneys were used for light & electron microscopic examinations, and morphometric study.Results: Light and electron microscopic examination andmorphometric studies revealed that metformin hydrochlorideinduced various signs of degeneration, necrosis, inflammationand fibrosis. Biochemical study revealed that metforminhydrochloride induced deterioration in the kidney functionswhich were reflected by significant increase in the serumlevels of urea and creatinine. On metformin hydrochloride withdrawal, most of the histological and all the biochemicaleffects were recovered specially in the second recovery groupwhere the recovery was directly proportionate with the duration of its withdrawal.Conclusion: Metformin hydrochloride induced variousdeleterious changes in the histological structure and functionof the kidney. These changes were improved on its withdrawal.