Cutaneous leishmanial lesions as well as serum samples from both infected human and Swiss-albino mice were used to investigate the role of Fas system (Fas-FasL) as an inducer of apoptosis and other leishmanicidal cytokines in the disease development in cutaneous leishmaniasis. Soluble Fas was estimated by ELISA, other leishmanicidal cytokines were detected by PAP technique and tissue Fas by RT-PCR. Results showed a significant increase in interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), nitric oxide (NO) and soluble Fas in both infected human and mice. As regards the tissue Fas, there was marked expression in human samples while in murine samples, the expression was reduced in chronic infected mice than in the late acute infected animals which can explain the progression of the lesion in the animals. This study confirms the role of Fas system as an inducer of apoptosis.