Objectives were to determine the effects recombinant bovine somatotropin (rbST) treatment during the peripartum period on hepatic mRNA expression of genes related to inflammation and immune response. Holstein cows were assigned randomly to receive no treatment (control; n = 10), 87.5 mg (rbST87.5; n = 12), or 125 mg (rbST125; n = 10) of rbST every 7 d from −21 to 21 d relative to calving. Liver biopsies were collected −21, −7, and 7 d relative to calving. Twenty-four genes were assessed by direct molecular counts using NanoString technology. Continuous data were analyzed by ANOVA. Gene expression on d −21 was used as a covariate for analyses of mRNA expression on d −7 and 7. No differences in mRNA expression were observed among treatments on d −21 for any of the genes except SOCS3, which had lower (P ≤ 0.05) mRNA expression in control cows compared with rbST87.5 cows. On d −7, expression of mRNA for ANGPTL4 and SCARB1 was higher (P ≤ 0.05) in rbST87.5 and rbST125 than control cows. The rbST87.5 cows had higher (P ≤ 0.05) mRNA expression for HP, ICAM1, SOCS2 and XBP1 on d −7 than control and rbST125 cows. Control cows had higher (P ≤ 0.05) mRNA expression for HIF1A than rbST125 cows on d −7. On d 7, control cows had higher (P ≤ 0.05) mRNA expression for CXCL1, IL1RN, MYD88, NFKBIA, and SOCS3 compared with rbST87.5 and rbST125 cows. Control cows had higher (P ≤ 0.05) mRNA expression for ICAM1 and XBP1 than rbST125 cows and had higher mRNA expression for HIF1A than rbST87.5 cows. Expression of mRNA for NR3C1 and SOCS2 was lower (P ≤ 0.05) in control cows than rbST125 and rbST87.5 cows, respectively. Treatment did not affect hepatic expression of CEBPD, JUN, M-CSF1, NFKB1, PPARGC1A, STAT5B, TLR2, TNF, TNFRSF1 and TNFRSF5. Weekly treatment of periparturient cows with rbST regulates liver mRNA expression of genes related to inflammation and immune response during the prepartum and postpartum periods. These rbST-induced changes in gene expression have resulted in improved neutrophil function, antibody production, and reduced incidence of retained placenta and metritis.