Abstract: Objective To investigate the effects of FFA on insulin secretion and expression of SUR1 gene in rat pancreatic β cells in vitro and its mechanism. Methods Pancreatic islet cells of rat were isolated, cultured and co-incubated with 0.25mmol/L palmitic acid (PA) and 0.125 mmol/L oleic acid (OA) respectively for 48 h. The released insulin was measured by radioimmunoassay. The SUR1 gene mRNA expression was quantified by RT-PCR. Results Compared with the control group, palmitic acid increased the basal insulin secretion by 110%(P<0.01), decreased the glucose-slimulated insulin secretion (GSIS) by 43%(P<0.01),while oleic acid increased the basal insulin secretion by 80%(P<0.01), decreased the GSIS by 32%(P<0.05). Only the oleic acid significantly suppressed the SUR1 gene expression by 64%(P<0.01), but PA had no effect on the gene expression (P>0.05), compared with the control group. Conclusions FFA inhibits GSIS. FFA′s regulation of SUR1 gene expression of β cells may be involved in the inhibiting effect.