The peroxisome proliferator-activated receptors (PPARs) and interferon γ (IFNγ) have a vital role in lipid homeostasis and immune functions respectively, and little is known about their beneficial role in kidney function during different seasons in catfish. We used immunohistochemistry for detection of cellular expression of PPARα, PPARγ, and IFNγ in the head kidney and posterior kidney of African catfish, we found that the PPARα and PPARγ in head kidney gave a positive reaction in melanomacrophage centers (MMC), large lymphocytes, red blood cells, endothelial cells, and connective tissue capsule. This positive reaction reached its highest at winter. While in the posterior kidney they were detected in the cytoplasm of epithelium lining renal tubules and the summer was the highest season in expression. However, IFNγ showed a positive reaction in the MMC and T-lymphocytes of the head kidney, which increased during the autumn season more than winter, spring and summer seasons. While in the posterior kidney its positive reaction was found in MMC, epithelial cells lining distal convoluted tubules and few in proximal convoluted tubules. The highest positive reaction in the posterior kidney was during the autumn season and was lowest in the summer season. This study established an essential role for both PPARs and IFNγ in immune and excretory functions of the kidney as well as, a reverse relationship between PPARs and IFNγ in the head and posterior kidneys of catfish.