Objective: Perform clinical and histopathological evaluations of gingival hyperplasia after kidney transplantation in patients receiving either cyclosporine (CsA) or tacrolimus (TAC). Subjects and Methods: A sample of 54 male renal transplant patients who have undergone immunosuppressive regimen (CsA=28 and TAC=26) were examined in respect to demographic, pharmacologic, and periodontal variables. Gingival overgrowth (GO) was assessed by using gingival enlargement index. In addition gingival biopsies were examined histopathologically with Hematoxylin and eosin (H&E) stain and Immunohistochemistry using caspase 3 expression and histomorphometric Analyses. Furthermore the serum level of matrix metalloproteinase (MMP2) was assessed in the two groups. Data were analyzed statistically using the Statistical Package for Social Sciences (SPSS). Results: Considering gingival enlargement, there was a statistically significant difference between (CsA) and (TAC) group's index with higher mean in (CsA) group versus (TAC) group. Considering the gingival bleeding index, there was a statistically significant difference between (CsA) and (TAC) groups with higher mean in (CsA) group versus (TAC) group and regarding serum (MMP2) level, there was statistically significant difference between (CsA) and (TAC) groups with lower mean in (CsA) group versus (TAC) group. Histopathologically, the degree of tacrolimus-influenced gingival enlargement was lesser in comparison to (CsA) group. Conclusions: (CsA) has a greater degree of gingival enlargement than (TAC) as shown clinically and histolopathologically but the serum level of (MMP2) was higher in (TAC) group than in the (CsA) group. (MMP2) may have a role in the mechanism of gingival enlargement.