Objective： To investigate the effect of Jiaotai Pill on SH-SY5Y cell injury induced by high glucose and high lipid. Methods： Twenty Sprague Dawley rats were randomly divided into control group and Jiaotai Pill group, with 10 rats in each group. The rats in the Jiaotai Pill group were given Jiaotai Pill solution 8.4 g·kg^-1 by gavage, and the rats in the control group were given normal saline by gavage for 7 consecutive days to prepare blank serum and Jiaotai Pill serum. SH-SY5Y cells were cultured in vitro and treated with different proportions of serum for 24 hours. CCK-8 assay was used to detect the effect of serum containing Jiaotai Pill on the proliferation of SH-SY5Y cells. The cells were and divided into control group, low dose group and high dose group, SIRT1 inhibitor EX527 group according to the proportion of drug-containing serum and cultured with 25 mmol·L^-1 high glucose and 200 μmol·L^-1 palmitic acid or normal medium. Endoplasmic reticulum (ER) associated proteins [inositol-requiring enzyme 1α(IRE1α), phospho-inositol-requiring enzyme 1α(p-IRE1α), protein kinase R-like endoplasmic reticulum kinase (PERK), phospho-protein kinase R-like endoplasmic reticulum kinase (p-PERK), activating transcription factor 6(ATF6) and glucose regulated protein 78 (GRP78)、protein disulfide isomerase（PDI）] were detected by Western blot. Immunofluorescence was used to detect the expression of energy metabolism-related proteins (SIRT1、p-IRE1α、 p-PERK) in each group. Results： Compared with the control group, GRP78, the ratio of p-PERK to PERK and the ratio of p-IRE1α to IRE1α were significantly increased in the model group (P<0.05), SIRT1 and PDI were significantly decreased (P<0.05). Compared with the model group, the expressions of SIRT1 and PDI were up-regulated (P<0.05), and the expressions of GRP78, p-PERK/PERK,and p-IRE1α/IRE1α were down-regulated (P<0.05) in a concentrationdependent way in Jiaotai Pill low and high concentration groups.EX527 group significantly reversed the effect of Jiaotai pill(P<0.05). Conclusion： The drug-containing serum of Jiaotai Pill improve the high glucose/palmitic acid induced injury of SH-SY5Y cells by improving SIRT1 and inhibiting endoplasmic reticulum stress.