The aim of this study was to determine whether 2,4-thiazolidinedione (2,4-TZD) influences the effects of peripheral insulin action in steers given recombinant bovine tumor necrosis factor (TNF) alpha (rbTNF). Steers were treated once daily for 9 d (d0 - d8) with either s.c. injection of rbTNF (2.5 microg/kg), rbTNF + i.v. injection of 2,4-TZD (2.0 mg/kg), or s.c. injection of saline (control). The plasma glucose, NEFA, and insulin concentrations in the rbTNF-treated group increased compared to those in the control and rbTNF + 2,4-TZD groups, whereas glucagon concentration decreased. A single i.v. injection of insulin (0.2 U/kg), glucose (112.5 mg/kg), or growth hormone (GH)-releasing hormone (GHRH) (0.25 microg/kg) was performed on d4, d6, and d8, respectively. In the insulin challenge, the net area under the glucose curve (AUC) was smaller in the rbTNF group than in the control and rbTNF + 2,4-TZD groups. In the glucose challenge, the net insulin AUC was smaller in rbTNF + 2,4-TZD group than in rbTNF group. In the GHRH challenge, there was no difference in GH responses to GHRH between the rbTNF and rbTNF + 2,4-TZD groups, respectively. We conclude that 2,4-TZD treatment partially reverses the impairment of peripheral insulin action caused by rbTNF injection in steers.