Nitric oxide (NO) has been implemented in various pathological processes. In the present study, 47 highly-oxygenated isopimarane-type and novel carbon framework staminane-type diterpenes isolated from Orthosiphon stamineus of Indonesia, Okinawa, Myanmar and Vietnam were evaluated for their inhibitory activity in NO production by lipopolysaccharide (LPS)-activated macrophage-like J774.1 cells. All the isolated diterpenes showed concentration-dependent inhibition of NO production in LPS-activated macrophage-like J774.1 cells, and based on the results, their structure-activity relationship were established.