Objective To research the performance qualification of whole-body plethysmography in SD rats with baclofen and aminophylline. Methods Totally 30 Sprague-Dawley rats were divided into three groups: control group, baclofen group, and aminophylline group. The baclofen and aminophylline group received a single dose of 30 mg / kg baclofen or aminophylline in the study. The tidal volume box(TVb), minute ventilation box(MVb), and respiratory rate ( f)were detected with whole-body plethysmography at before dosing and 1 h, 2 h, 4 h after dosing. And tested the stability of the system through repeated the study twice. Results Control group had no significant change on the respiratory parameters.Compared with control group, TVb of the baclofen group increased significantly at 1, 2, 4 h after dosing(P< 0. 05), And f decreased at 1, 2, 4 h after dosing ( P< 0. 05). F and MVb of the aminophylline group increased significantly at 1, 2, 4 h after dosing(P< 0. 05). The result of two repeated studies were consistent with the first data. Conclusions The whole-body plethysmography can detect relevant changes in the respiratory system in SD rats after dosing. It can be used in conducting respiratory safety pharmacological investigation.