In this study, it was aimed to investigate whether 4-methylcatechol (4-MC) could serve as an autocrine antiapoptotic agent by increasing nerve growth factor (NGF) in beta cells of hyperglycemic rats. Rats were divided into four groups: the first group was given citrate buffer and saline, the second group was administered 4-MC, the third group received streptozotocin (STZ), and the fourth group was given both 4-MC and STZ. 4-MC (10 mu g/kg) was administered by daily intraperitoneal injection for 10 days before the animals were rendered hyperglycemic by administration of STZ (75 mg/kg). With 4-MC pretreatment on hyperglycemic rats the following results were noted: (i) Increase in plasma glucose, beta cell apoptosis and caspase-8 activation was prevented. (ii) Reduction of NGF(+) and tyrosine receptor kinase A (TrkA)(+) beta cell number was blocked. (iii) p75 neurotrophin receptor (p75(NTR))(+) beta cell number was increased. These data suggest that 4-MC might exert its antiapoptotic actions through NGF/TrkA system which may block NGF/p75(NTR) activation in pancreatic beta cells of hyperglycemic rats. (C) 2011 Elsevier Ltd. All rights reserved.