The present study investigated the protective effect of misoprostol (MSP) (0.2 mg/kg, oral) against kidney injury caused by paclitaxel (PLX) (2 mg/kg, intraperitoneal) in female Sprague Dawley rats. Twenty-eight 8-week-old rats were used and divided randomly into four equal groups (n = 7): control, MSP, PLX, and PLX+MSP. Malondialdehyde (MDA) level, serum creatinine (Cr), and blood urea nitrogen (BUN) were significantly increased in the PLX group compared to the control group (p < 0.05), while superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) were decreased (p < 0.05). In the PLX+MSP group, levels of serum Cr, and BUN were significantly decreased than the MSP group (p < 0.05). Further, lower level of MDA, and higher activity of GSH, SOD, and CAT was detected in the PLX+MSP than the PLX group (p < 0.05). In the PLX group, we also found a significant decrease in the total number of glomeruli and the mean volumes of cortex, medulla, and kidney compared to the control group (p < 0.05). Besides, these stereological parameters were improved in the PLX+MSP group than the PLX group (p < 0.05). We speculated that administration of MSP attenuated the toxic effect of PLX on kidney tissue due to its antioxidative and anti-apoptotic efficacy of MSP.