A time-adjustable pulsatile release system (TAPS) containing ketoprofen (KF) as an active pharmaceutical agent was developed having been designed for bedtime dosing and releasing drug in the early morning to control the symptoms of rheumatoid arthritis (RA). The formulation involved a tablet core (KF) and a control-release layer, and the coating membrane was composed of EC and Eudragit L100. A single-factor study, a central composite design and a response surface method were selected to optimize the formula and the optimum prescription was as follows: tablet core (KF 50 mg, MCC 70 mg, lactose 40 mg, L-HPC 38 mg), and film (EC 7.8 g, Eudragit L100 4.2 g, PEG 6000 1.8 g in 95% alcohol each 200 ml). The in vivo release behavior of the tablets was evaluated in Beagle dogs after a parallel oral administration of KF TAPS tablets and commercial KF capsules, when it was found that the KF TAPS tablets released the drug after a lag-time of 3.458 h and the Tmax was 5.833 h. The relative bioavailability was 85.01%, and the two formulations were bioequivalent in terms of Cmax and AUC0–t and the in vitro- in vivo correlations indicated that test formulation had a good in vivo-in vitro correlation (r = 0.9703). These results show that the novel drug delivery system (TAPS) has the potential to be used as a KF preparation with chronophamacokinetics characteristics.