This study aimed to investigate the stimulatory effect of glucagon-like peptide 1 (GLP-1) receptor agonist (GLP-1RA) on the apoptosis of hepatic stellate cells (HSCs) activated by high glucose, and to explore the underlying molecular mechanism with a focus on the c-Jun N-terminal kinase (JNK) and extracellular signal-related kinase (ERK) signaling pathways. Human HSCs were cultured in-vitro and their morphological features were identified. HSC samples were randomly collected and divided into a control group, GLP-1RA group, GLP-1RA+JNK blockade group, and ERK blockade group. The apoptosis of HSCs in each group were analyzed by fluorescence-activated cell sorting (FACS) after 120 h of culture. Phosphorylated JNK and ERK (p-JNK and p-ERK) proteins were detected by western blotting. p-JNK expression was higher in the GLP-1RA group compared with that of the control group and the GLP-1RA+JNK blockade group (both P<0.01). The apoptosis rate was higher in the GLP-1RA group compared with that of the control group and GLP-1RA+JNK blockade group (both P<0.01). p-ERK expression was lower in the GLP-1RA group and ERK blockade group than in the control group (both P<0.01). The apoptosis rates in the GLP-1RA group and ERK blockade group were higher than that of the control group (both P<0.01). GLP-1RA can promote the apoptosis of high glucose-activated HSCs through activation of the JNK signal pathway and through blocking the ERK signal pathway.