Background: Tumor necrosis factor-alpha is the key inflammatory cytokine in psoriasis vulgaris triggering abnormal differentiation and proliferation of keratinocytes. Etanercept as an antitumor necrosis factor-alpha agent is widely used for the treatment of psoriasis vulgaris. Objectives: To find out whether etanercept has an apoptotic effect on psoriatic keratinocytes. Methods: Biopsies from 13 untreated chronic plaque psoriasis patients and 10 control subjects were examined in the study. Immunohistochemical staining for Ki-67 and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL) method for the detection of apoptosis were performed. Ki-67 and TUNEL indices were calculated. Results: The mean Ki-67 index of patients before treatment (34.20 +/- 10.30) was significantly higher than that of the control subjects (8.30 +/- 2.20) and of the treated patients (9.50 +/- 2.50); however, it did not differ between the treated patients and control subjects (p < 0.001, p = 0.001 and p = 0.208, respectively). Although the mean TUNEL index of patients before treatment (0.23 +/- 0.44) was significantly lower than the controls (1.1 +/- 0.99), it did not significantly differ after etanercept therapy (0.46 +/- 0.66) (p = 0.030 and p = 0.083, respectively). The mean TUNEL indices of treated patients and control subjects were not different (p = 0.131). Conclusion: Etanercept decreased epidermal thickness successfully without inducing apoptosis of psoriatic keratinocytes.