OBJECTIVE To detect the differences in gene expression of brain tissue in septic rats with ulinastatin (UTI) preconditioning with DNA microarray. METHODS Forty-five male Wistar rats were equally divided into control group, sepsis group, and UTI group by means of random number table. In UTI group the rats were treated with intramuscular injection of UTI (100 kU/kg) 1 hour before cecal ligation and puncture (CLP). In sepsis group and control group intramuscular balanced solution (5 ml/kg) instead of UTI was given. Septic rat model was reproduced by CLP. The control group underwent a simulated operation without CLP. Gene expression profile was studied by using RatRef-12 rat gene expression profile microarray to detect the changes in gene expression pattern of rat brain tissue after CLP. Then related computer software was used to screen and analyze the relationship between the sepsis/UTI group and control group. Finally, the difference between the sepsis group and UTI group was analyzed. RESULTS In 22 523 genes, 55 differential genes were found between sepsis group and control group, accounting for 0.244%. Among them 47 genes showed down-regulation, with 23 known functional genes; 8 genes showed up-regulation, with 6 known functional genes. Eighty-two differential genes were found between UTI group and control group, accounting for 0.364%. Among them 66 genes showed down-regulation, with 39 known functional genes; 16 genes showed up-regulation, with 8 known functional genes. When sepsis group and UTI group compared with control group, 19 genes showed the same degree of regulation,with 18 genes (Adora2a, Avp, Cart, Gng7, Myh7, Oxt, Pde1b, Pdyn, Prkcd, Prkch, Rgs9, Rxrg, Six3, Slc17a6, Slco1a5, Sostdc1, Tac1, Ttr) showed down-regulation and 1 gene (S100a8) showed up-regulation. CONCLUSION UTI preconditioning can partly adjust abnormal expression of genes in the brain tissue of rat with sepsis in the presence of excessive inflammation and immune suppression. UTI has some degree of protective effect on brain at the genetic level. Meanwhile, there is certain self regulation in the body during sepsis.