Context: Rheumatoid arthritis (RA) is differentiated as an early morning exacerbation of the core arthritis condition associated with increase in pain and stiffness in joints and necessitate for medication. Objective: The aim of the present work was to develop and optimise a pH-triggered delayed-release colon-specific aceclofenac microspheres and to accomplish chronotherapy of RA. Methods: A 3-factor, 3-level Box-Behnken design (BBD) was used to optimise selected variables. Developed formulation was evaluated for in vivo delayed response and anti-arthritis activity in rats. Results: The particle size and encapsulation efficacy of these microspheres were 117.36 +/- 10.54 mm and 85.06 +/- 5.85%, respectively. Optimised formulation was analysed by SEM, DSC, X-RPD and FTIR. The in vivo evaluation reveled delayed anti-inflammatory activity in carrageenan-induced rats and anti-arthritic activity in freund's adjuvant-induced arthritis rats. Conclusion: The optimised aceclofenac microspheres formulation is potential for the chronotherapy of early morning symptoms of RA.