Trauma/hemorrhagic shock (TH/S) has been associated with inflammation and immunodisorders, leading to immunosuppression, multiorgan dysfunction, and death. However, little is known about the effect of resuscitation with different solutions on the immunological function. To address this issue, groups of male Sprague-Dawley rats were induced with TH/S by fracture in the left femur and continual bleeding to keep the MAP of 30 ± 5 mmHg for 30 min, followed by resuscitation with 6% hydroxyethyl starch solution (HES), Ringer's lactate solution (RS), or 5% albumin (ALB), and the impact of resuscitation on the activation, differentiation, and survival of CD4+ T cells was longitudinally examined after TH/S and resuscitation. After resuscitation, the MAP, as expected, gradually increased regardless of the type of fluids transfused. The percentage of CD4+ T cells decreased to 20% to 25%, and the ratio of T helper type 1 (TH1)/TH2 responses was significantly reduced in all TH/S rats, however, resuscitation with HES alone reversed the trends (49.4% ± 9.7% vs. 55.2% ± 2.6% in sham for CD4+ T cells; 0.64 ± 0.23 vs. 0.71 ± 0.16 in sham for the ratio of TH1/TH2, P > 0.05 for both). Treatment with HES or ALB, but not RS, prevented CD4+ T-cell apoptosis (sham, 7.23% ± 3.4%; HES, 10.2% ± 4.1%; RS, 15.2% ± 5.4%; ALB, 10.6% ± 4.3%; 48 h) and nuclear factor-κB p65 activation (sham, 0.17 ± 0.04; HES, 0.34 ± 0.05; RS, 0.41 ± 0.09; ALB, 0.25 ± 0.09; 48 h) induced by TH/S early after resuscitation. These data demonstrated that HES resuscitation modulated the balance of TH1 and TH2 responses and inhibited TH/S-related nuclear factor-κB activation and CD4+ T-cell apoptosis in TH/S rats. Our findings provide new insights into understanding the TH/S-related immunodisorders and may aid in the design of new therapy for intervention of TH/S.