Background: Depression is a mood disorder that causes a persistent feeling of sadness and loss of interest. Platelet rich plasma (PRP) is an autologous derivative of the whole blood which has an important regenerative role in medicine. Materials and Methods: Thirty adult male albino rats were used in this study. They divided into three groups: control, flouxetine and platelet rich plasma treated groups. Results: There was statistically significant difference between the studied groups regarding creatinine level, MDA, IL6 and TNF with the highest level was reported in the fluoxetine group. The renal cortex of fluoxetine treated group showed congested glomerular capillaries. Some tubular cells had dark stained nuclei. Massive interstitial infiltration of inflammatory cells was detected in some sections. PRP treated group showed marked improvement in the histological structure of renal cortical tissue. Sections of fluoxetine treated group revealed a few PAS positive reaction at the brush border of most of PCT and the basal lamina of the tubular cells, that returned as the control group in PRP treated group. In fluoxetine treated group cytoplasmic positive reaction in fluoxetine treated group was seen in many epithelial lining of the tubules positive immunoreactions in few tubules PRP treated group. Conclusion: our study found that fluoxetine causes deterioration of the kidney function and changes in histological structure of renal cortex which were improved by PRP application which were improved by PRP application.