Abstract: In order to investigate whether CDK5 could participate in the coat color formation of alpaca, the regulation of CDK5 on TYR and MITF expression in alpaca melanocytes was tested in this study. The localization of CDK5 in cultured alpaca melanocytes was examined by immunohistochemistry. Then CDK5 was transfected into cultured alpaca melanocytes by liposomes. Following the transfection, CDK5 protein was detected by Western blot and the expression of MITF and TYR was detected by quantitative realtime PCR(qRTPCR). The immunohistochemistry results showed that CDK5 was expressed in cytoplasm and nucleus of cultured alpaca melanocytes; Western blot results showed that the level of CDK5 protein was apparently higher in transfected melanocytes than that in normal melanocytes, and qRTPCR results showed that the mRNA abundance of MITF was downregulated while the mRNA abundance of TYR was upregulated by the transfection with CDK5, and the expression level of MITF and TYR mRNA in transfected melanocytes was 0.264 9 and 3.931 3 folds higher than that in controlled melanocytes respectively. The results suggest that CDK5 participate in the formation of coat color by regulating TYR and MITF expression in alpaca melanocytes.