<i>Background:</i> Scarring is one of the steps of excessive wound healing, causing dysfunction of the involved tissues and clinically poor cosmetics. The aim of this study was to examine the effect of a highly selective cyclooxygenase-2 (COX-2) inhibitor on renal scar formation in experimental pyelonephritis. <i>Materials and Methods:</i> Four groups of 10 Balb/C mice were formed. In groups I and II following the inoculation of lipopolysaccharide (LPS) into both kidneys, 0.18 and 0.36 mg/day of rofecoxib was given respectively via intraperitoneal route for 5 days. No medication was applied following physiological saline solution injection to both kidneys of the mice in group III (negative control group). After group IV’s LPS inoculation on the first day, saline solution (1 ml/day) was given intraperitoneally for 5 days (positive control group). Following the exposure of both kidneys, LPS of <i>Escherichia coli</i> (5 mg/kg) was injected into the kidneys of groups I, II, and IV. In group III, saline solution (0.1 ml) was used instead of LPS. Three days after the inoculation of LPS, solutions containing 0.18 and 0.36 mg of COX-2 inhibitor were given intraperitoneally for 5 days in groups I and II. No medication was used for the mice in group III. Six weeks after the inoculation of LPS and saline solution, all mice were humanely euthanized. Bilateral nephrectomies were done on each group of mice, and histopathological examination was performed. <i>Results:</i> Inoculation of LPS into the renal parenchyma caused pyelonephritis and scar formation in all groups. The degree of pyelonephritis and scar formation was lesser in groups in which COX-2 inhibitors were used. The degree of scar formation was lesser in group II, in which 0.36 mg more of COX-2 inhibitor was used than in group I (0.18 mg of COX-2 inhibitor). <i>Conclusion:</i> In our study model, direct inoculation of LPS to kidneys caused experimentally induced pyelonephritis. Renal scar formation was effectively prevented through the utilization of rofecoxib at 0.36-mg doses.