Objective To study the application of implantable telemetry and whole-body plethysmography to observe the changes of circadian rhythm in conscious rats and evaluate the pharmacological safety of doxofylline, and to provide a basis for the future application of this technological system for drug safety evaluation. Methods Eight healthy SPF Sprague-Dawley rats were used in this study, 4 males and 4 females. The rats were implanted with telemetry transmitters by surgery to establish a telemetry system combined with plethysmography to observe the changes of 24 h physiological parameters and circadian rhythm in conscious rats at 14 d after operation, including heart rate (HR), blood pressure, the time interval from the Q wave to point A in the ECG of the aortic pressure wave (QA interval), respiration, activity, body temperature and pulmonary function parameters. The rats were divided into 3 groups:normal control group, doxofylline 40 mg/kg and 80 mg/kg groups, and the performance was validated by aerosolizing saline, doxofylline 40 mg/kg and 80 mg/kg inhalation, respectively, to observe the changes in physiological parameters after the drug administration. Results The physiological parameters of rats showed obvious changes in circadian rhythms at 14 d after operation. Compared with the normal control group, the doxofylline 40 mg/kg-treated group showed significantly increased changes of HR, tidal volume (TV), minute ventilation (MV), 50% expiratory flow (EF50), peak inspiratory flow (PIF) and peak expiratory flow (PEF) (P<0.01), significantly decreased respiratory frequency, QA interval and enhance pause (Penh) (P<0.05, P<0.01), but no significant differences in the blood pressure, activity and body temperature (P>0.05). Compared with the normal control group, the group treated with doxofylline 80 mg/kg had significantly increased HR, blood pressure, TV, MV, EF50, PIF and PEF (P<0.01), significantly decreased respiratory frequency, QA interval and Penh not (P<0.01), but not significantly changed activity and body temperature (P>0.05). Conclusions The application of implantable telemetry and whole-body plethysmography in this study does not obviously affect the circadian rhythm, and can sensitively monitor the relevant cardiovascular and respiratory parameters in conscious rats. It can be used in drug safety pharmacological research of cardiovascular and respiratory systems in conscious rats.