Abstract The aim of the present study was to determine the profile of p53 protein expression in gingival tissues after treatment with nifedipine in rats. Rats were treated daily by gastric intubation with or without DMSO alone or DMSO-dissolved nifedipine at concentrations of 15, 30 or 60 mg/kg body weight for 1, 3 or 6 week(s). Gingival width and height were measured macroscopically. Monoclonal antibodies recognizing both wild-type and mutant p53 protein were applied on paraffin-embedded gingival sections using microwave pretreatment and immunohistochemical methods. The gingival width and height were increased in the animals treated with nifedipine at concentrations of 30 and 60 mg/kg body weight. Increased gingival width and height were already seen in the animals treated with 60 mg of nifedipine for 1 week, whereas treatments with 30 mg of nifedipine resulted in increased gingival width and height after treatment for at least 3 weeks. The expression of p53 protein was elevated in the animals treated with 30 or 60 mg of nifedipine. Treatments with nifedipine at the concentration of 60 mg/kg body weight for 1 week induced the expression of p53 protein in the gingival tissues. Treatment with nifedipine in rats led to the inducement of gingival hyperplasia and increase in the numbers of p53-positive gingival epithelial cells by a dose and frequency dependent mechanism, suggesting that p53 protein may play a crucial role in the regulation of nifedipine-induced gingival hyperplasia.