PPAR-alpha is a ligand-activated transcription factor belonging to the nuclear receptor superfamily, involved in the regulation of in vivo triglyceride levels, presumably through its effects on fatty acid and lipoprotein metabolism. Some nuclear receptors have been involved in rapid effects, mediated by non-genomic mechanisms. In this work, we study the non-genomic effects of PPAR-alpha in the endocrine pancreas. For this we use freshly isolated islets of Langerhans from adult male mice and perform intracellular calcium concentration measurements, immunocytochemistry and insulin secretion quantification by RIA. The main effect of the endogenous PPAR-alpha agonist OEA in pancreatic beta-cells is a rapid decrease in glucose-induced calcium oscillations in a dose-dependent manner. This effect is mimicked by the specific agonists WY14643 and GW7647. This effect is still produced in the presence of the protein and mRNA synthesis inhibitors cycloheximide and actynomicin D, which suggests that it is independent of gene transcription. Parallel, the PPAR-alpha agonist WY14643 produces a decrease in glucose-induced insulin secretion. PPAR-alpha is present in beta-cells mainly in cytosol and nuclei, with a small subpopulation localized in the plasma membrane. The use of mice which PPAR-alpha gene possesses an insertion in the exon encoding the transactivation domain 2, suggests that the rapid effect of the agonists of PPAR-alpha on insulin secretion is independent of the its function as transcription factor. We can conclude that agonists of PPAR-alpha produce a decrease in insulin secretion in beta-cells through a non-genomic mechanism.