© 2018 Govi-Verlag Pharmazeutischer Verlag GmbH. All rights reserved. The ischemia/reperfusion (I/R) process alters metabolic pathways, releasing reactive oxygen species and pro-inflammatory cytokines that cause tissue necrosis and activate cellular apoptotic pathways. Misoprostol (MSP) is a prostaglandin E1 analog that has demonstrated a cytoprotective role in the I/R process. The study objective was to evaluate the effects of MSP on the regulation of pro-inflammatory and oxidative stress mediators in an I/R-induced acute kidney injury rat model. Wistar rats were divided into 3 groups. Sham and I/R were given 1 mL/day of physiological solution; MSP+I/R was given intragastric MSP (300 μg/kg) for 3 days. For I/R and MSP+IR, the renal hilum was clamped for 45 min, followed by 15 h of reperfusion. Renal function tests, pro-inflammatory cytokines, mediators of oxidative stress, and histological analysis were evaluated. Pro-inflammatory cytokine activity was significantly attenuated in the MSP+I/R group. However, there was no statistically significant difference between Sham and MSP. Regarding antioxidant activity, MSP+I/R showed a significant decrease in these mediators compared with Sham and I/R. Histologically, scarce medullary necrosis was observed with a preserved renal cortex in the MSP group.