Twenty-eight pyrazoline derivatives, which originated from pyranochalcones, have been synthesized and evaluated for their inhibitory potency on the production of inflammatory mediator nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. Among them, three compounds (1c, 11c, and 15c) exhibited potent inhibitory effects on NO production and iNOS activity superior to positive control Indomethacin, with 1c being most efficacious. Furthermore, 1c could suppress the progress of carrageenan-induced hind paw edema at a dosage of 50 mg/kg/day and dose-dependently ameliorate the development of adjuvant-induced arthritis (AIA). Docking study confirmed that 1c was an iNOS inhibitor with good binding into the active site of murine iNOS.