Objective: To determine the protective effects of hyaluronic acid and chondroitin sulfate in treating urinary tract infections in a rat model. Methods: A total of 28 rats, which were induced with urinary tract infections through intravesical administration of Escherichia coli, were included in the study. By random selection, they were equally divided into four groups as control (no treatment), hyaluronic acid, chondroitin sulfate and hyaluronic acid + chondroitin sulfate. Bacteriological cultures of the urine and bladder tissue samples were carried out, and the data for each group were statistically compared. Results: In the urine cultures, there were significant differences in median bacterial growth rates in hyaluronic acid (5 x 103 cfu/mL) and chondroitin sulfate (1 x 104 cfu/mL) groups relative to the control group (5 x 104 cfu/mL). However, a significantly lower rate of bacterial colony growth was observed in the hyaluronic acid + chondroitin sulfate group (8 x 102 cfu/mL; P < 0.05). In the bladder tissues, statistically significant decreases in median bacterial growth rates were detected in the hyaluronic acid and hyaluronic acid + chondroitin sulfate groups (both 0 cfu/mg tissue; P < 0.05). Also, transitional epithelium damage decreased in the treatment groups. However, this effect was prominent in hyaluronic acid + chondroitin sulfate group. Conclusion: Our experimental findings show that the hyaluronic acid + chondroitin sulfate combination has a potential benefit in reducing the bacterial load in urine and the thickness of the transitional epithelium.