By studying the effect of Buzhong Yiqi Decoction（补中益气汤）on the endoplasmic reticulum stress of A549 cells and A549/DDP cells through Nrf2/ROSpathway，the molecular mechanism of Buzhong Yiqi Decoction improving cisplatin resistance in non-small cell lung cancer was investigated.

The serum containing Buzhong Yiqi Decoction was prepared and A549 cells and A549/DDP cells were cultured. They were randomly divided into group A（A549 cells），Group B（A549 cells+20μg/mL cisplatin），group C（A549 cells+20μg/mL cisplatin+10% Buzhong Yiqi Decoction-containing serum），group D（A549/DDP cells），group E（A549/DDP cells+20μg/mL cisplatin）and group F（A549/DDP cells+20μg/mL cisplatin+10% Buzhong Yiqi Decoction-containing serum）. Half inhibitory concentration of cisplatin（IC₅₀）was detected by CCK-8 method，and reactive oxygen species（ROS）were detected by DCFH-DA fluorescent probe method. The protein expression levels of Nrf2，P-Nrf2，PERK，P-PERK，eIF2α，P-eIF2α，IRE1 and XBP1 were detected by Western blot.

In both A549 cells and A549/DDP cells，Buzhong Yiqi Decoction significantly decreased the IC₅₀ value of cisplatin（P<0.05）. In both cells，cisplatin could up-regulate the protein expressions of Nrf2 and P-Nrf2，and after the intervention of Buzhong Yiqi Decoction，the expression levels of both were down-regulated（P<0.05）in A549/DDPcells compared with those in A549 cells（P<0.05）. Compared with the blank group，cisplatin could up-regulate the ROSexpression of the two cells（P<0.05），the ROS expression was further up-regulated after combined with Buzhong Yiqi Decoction（P<0.05），and the ROSexpression level of A549 cells was significantly higher than that of A549/DDP cells（P<0.05）. There were no significant differences in the expressions of PERK and eIF2αamong all groups（P>0.05）. Cisplatin significantly up-regulated the protein expressions of PPERK，P-eIF2α，IRE1 and XBP1 in the two cell lines，and the expression was up-regulated again after the intervention of Buzhong Yiqi Decoction（P<0.05），and the expression of ER stress protein in A549 cells was higher than that in A549/DDP cells（P<0.05）.

Buzhong Yiqi Decoction may improve cisplatin resistance of A549 cells and A549/DDP cells by regulating ERSthrough Nrf2/ROSsignal pathway.