Background and Aim: The soft coral genus Sarcophyton is a source of cembraneterpen. Sarcophyton is reported to have anti-inflammatory properties, with the ability to reduce the expression of inducible nitric oxide synthase (iNOS) and inhibit nuclear factor-kappa B (NF-B) activation. This study aimed to investigate the efficacy of dichloromethane (DCM) extracts of soft coral Sarcophyton spp. to inhibit the expression of NF-B and iNOS induced by lipopolysaccharide (LPS). Materials and Methods: Crude extracts of Sarcophyton spp. were macerated with DCM (1:3 v/v) for 24 h. Thirty-six Balb/c mice were divided into six treatment groups, namely, normal control (without LPS induction), negative control (LPS induction 4 mg/mL), comparative control (LPS+Dexamethasone 6 mg/kg), and 3 concentration groups extract (LPS+50, 125, and 250 mg/kg). The expression of NF-B and iNOS was measured in each treatment group. Results: Flow cytometry analysis showed that the relative number of NF-B+ cells increased (18.381.24%) in LPSinduced mice compared with normal mice (13.241.15%). The Sarcophyton spp. DCM extracts decreased the relative number of NF-B+ cells (125 mg/kg: 13.960.84%). Immunohistochemical analysis with ImmunoMembrane showed that LPS induction in mice increased iNOS expression when compared to normal mice. The Sarcophyton spp. DCM extracts reduced iNOS expression (especially at 125 mg/kg). Conclusion: DCM extracts of Sarcophyton spp. inhibited the activation of NF-B, resulting in suppressed iNOS expression, which directly inhibits NO production.