Objectives:Gingival overgrowth is an infrequent side effect with tacrolimus when compared to cyclosporine. The exact mechanism underlying this is not fully understood. The study was aimed to compare the collagen content, levels of MMP-1, MMP-2 and TIMP-1 in cyclosporine and tacrolimus induced gingival overgrowth in rats. Methods:A total of eighteen, 21 days old male wistar rats were assigned to three group of six each. Group-1 (control) __ampersandsignndash; Administration of olive oil daily, Group-2 __ampersandsignndash; Administration of cyclosporine 30 mg / kg body weight in olive oil, Group-3 __ampersandsignndash; administration of tacrolimus 1.5 mg / kg body weight in olive oil. Gingival tissues were collected after 30 days from incisor region and total collagen content was calculated from hydroxyproline estimation. SDS-PAGE zymography was used to obtain zymogram profiles of MMP-1 and MMP-2. Western blot analysis was performed to confirm the expression MMPs and TIMP-1. ELISA was used to quantify the expression of MMPs and TIMP-1. Mean values were compared by oneway ANOVA followed by Tukey-HSD procedure. Results:Collagen content was significantly higher in Group-2 with no significant difference between Groups-1 and 3. MMP-1, MMP-2 were significantly reduced in Group-2 but was significantly higher in Group-3 compared to Group-1. TIMP-1 was highest in Group-2 but Group-3 also showed higher level compared to Group-1. Conclusion:Cyclosporine increases the collagen content and reduces MMP-1 and MMP-2 whereas tacrolimus doesn__ampersandsignlsquo;t alter collagen content but increases MMP-1 and MMP-2 and cyclosporine increases TIMP-1 more than in rats.