The nephrotoxicity induced by methotrexate is a severe condition that greatly affects its therapeutic potential and has a significant inflammatory component. Fimasartan is an angiotensin receptor blocker that offers organ-protective effects and may be useful in mitigating renal injury. The present study explored the anti-inflammatory potential of two doses of fimasartan against methotrexate-mediated nephrotoxicity. Albino rats were intraperitoneally administered a single methotrexate (20 mg/kg). Intraperitoneal treatment with fimasartan (5 or 10 mg/kg/day) was initiated on day two after methotrexate injection and continued for seven consecutive days. Methotrexate significantly increased serum urea, creatinine, and NGAL concentrations. It also substantially elevates the proinflammatory cytokines (namely, tumour necrosis factor-alpha, interleukin-1 beta, and interleukin-6) levels while reducing renal tissue’s immunomodulatory (interleukin-10) levels. Treatment with both doses of fimasartan significantly restored renal function parameters, lowered the renal concentration of proinflammatory cytokines, and upregulated the renal concentration of the anti-inflammatory mediator interleukin-10. The high fimasartan dose resulted in more pronounced effects on the inflammatory parameters. The obtained data suggested that fimasartan effectively mitigates methotrexate-induced nephrotoxicity by inhibiting inflammation in renal tissue in a dose-dependent manner.