Mitogen-activated protein kinase (MAPK) signal transduction pathways may be involved in the destruction of pancreatic islet beta cells induced by inflammatory cytokines. The present study aimed to investigate the role of different MAPK signal transduction pathways in the interleukin-1 beta (IL-1 beta)-induced inhibition of glucose-stimulated insulin secretion (GSIS) in Min6 mouse pancreatic cells. Min6 cells were stimulated with different concentrations of glucose (0.0, 5.5, 11.1 and 22.2 mmol/l), or different concentrations of IL-1 beta (0.00, 0.25 and 2.50 ng/ml) in combination with high glucose (22.2 mmol/l) and the culture supernatant was collected. The concentration of insulin was measured by enzyme-linked immunosorbent assay and the activation of different MAPK pathways was assessed by measuring the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-jun N-terminal kinase (JNK) via western blotting. The production of reactive oxygen species (ROS) was determined via flow cytometry, and cell viability was detected by Cell Counting Kit-8 assay. Reverse transcription-quantitative PCR was used to detect the insulin 1 gene. The results revealed that glucose activated ERK1/2 phosphorylation, but inhibited JNK and p38 phosphorylation in a concentration-dependent manner. Furthermore, IL-1 beta inhibited glucose-stimulated insulin secretion in a dose-dependent manner. Western blotting revealed that IL-1 beta inhibited the activation of ERK1/2 phosphorylation and attenuated the inhibition of p38 phosphorylation induced by glucose stimulation. JNK was neither activated nor inhibited by IL-1 beta. These results suggest that MAPK signal transduction pathways participated in the IL-1 beta -induced GSIS inhibition in Min6 cells, with the ERK1/2, JNK and p38 signaling pathways playing different roles.