The tuberous root of Tinospora sagittata (Oliv.) Gagnep is the original plant of Traditional Chinese Medicine Tinosporae Radix (“Jin Guo Lan”), which usually be used to treat pharyngeal arthralgia, carbuncle furuncle, bacillary dysentery, abdominal pain and inflammation. Twenty-six clerodane diterpenoids were isolated from T. sagittata, including 8 new clerodane diterpenoids (tinotanoid A-H: 1-8), and 18 known ones (9-26). The absolute configurations of compounds 1, 2, 5, 8, 13, 17 and 20 were determined by single-crystal X-ray diffraction. Compound 1 is the first example of clerodane diterpenoid with a γ lactone ring which were constructed between C-11 and C-17. Compound 2 and 17 is a pair of epimer. Compounds 2, 12 and 17 showed excellent inhibitory activity on NO production with IC50 values of 9.56±0.69, 9.11±0.53 and 11.12±0.70 μM, respectively, and the activities were significantly stronger than the positive control Minocycline (Mino) (IC50 value was 23.57±0.92 μM). Moreover, compounds 2, 12 and 17 dramatically reduced the expressions of iNOS and COX-2 up-regulated by LPS treatment. Compounds 2 and 12 can significantly inhibit the levels of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 that are increased by LPS stimulation.