AIM: To explore the possibility that expressions of different heat shock proteins (HSPs) are specifically involved in the protection of thermal preconditioning against apoptosis of cerebellar granule neurons (CGNs) induced by repolarization. METHODS: Western blotting was used to detect expressions of HSP27, HSP70, and HSP90 induced by thermal preconditioning (TP) in CGNs; reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression level of HSP70 mRNA; apoptosis of CGNs was induced by switching culture medium containing KCl 25 mmol/L to one containing KCl 5 mmol/L. RESULTS: No expression of HSP27 in cerebellar granule neurons was observed with TP at 44 ºC. Expression of HSP90 was obvious in CGNs both without and with TP at 44 ºC for different periods. Expression of HSP70 protein in CGNs was lower with TP at 44 ºC for 5 min, but it increased gradually after the period was prolonged to 30, 60, or 90 min. HSP70 mRNA was detected after TP 44 ºC for 30, 60, and 90 min and increased gradually with time. HSP70 antisense oligodeoxynucleotides 10 μmol/L for 72 h inhibited the protective effects of TP at 44 ºC on apoptosis of CGNs induced by repolarization. CONCLUSION: HSP70 is involved in protective effects of thermal preconditioning on apoptosis in cerebellar granule neurons induced by repolarization.