The rat insulin promoter (RIP) has been used to drive the expression of Cre recombinase (Cre) specifically in beta cells. Transient transfection was performed in the mouse insulinoma cell line, NIT-1, and control cell lines. RT-PCR was performed using total RNA from pancreas and other tissues of RIP-Cre transgenic mice. In addition, the efficiency and specificity of RIP were further analyzed by cross breeding the RIP-Cre transgenic mice with reporter mice bearing a beta-actin-loxP-CAT-loxP-lacZ transgene. In these mice, lacZ is expressed only after excision of the floxed-CAT gene by Cre-mediated recombination. Here, we present the data for beta cell-specific expression of lacZ in bigenic mice, as proof of concept in a mouse model for targeting beta cell-specific gene(s). The RIP-Cre transgenic mice will be used as a potential tool for targeting the excision of beta cell-specific gene(s) to study their role in islet cell physiology.