This study aimed to explore the anti-inflammatory effect of four lupane-type triterpenoids from Acanthopanax gracilistylus on lipopolysaccharide-induced RAW 264.7 cells. The lupane-type triterpenoids were impressic acid (1), 3α, 11α-dihydroxy-23-oxo-lup-20(29)-en-28-oic acid (2), 3α, 11α, 23-trihydroxy-lup-20(29)-en-28-oic acid (3), 3α-hydroxy-lup-20(29)-en-23,28-dioic acid (4). RAW 264.7 cells were stimulated by lipopolysaccharide to establish an inflammatory model. The level of nitric oxide was determined by Griess. The levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were determined by ELISA. The expression of high-mobility group box 1 protein (HMGB1) was detected by Western blot. The expressions of TNF-α and IL-1β mRNA were detected by RT-PCR. The levels of nuclear factor-κB (NF-κB) were measured by ELISA. The results showed that, compared with the model group, compound 1 and 4 could significantly reduce the release of NO, TNF-α, and IL-1β; compound 2 could inhibit the production of NO and IL-1β; compounds 1, 2 and 4 could inhibit the secretion of HMGB1 by cells; compounds 1 and 4 had a significant inhibitory effect on the mRNA expression of TNF-α induced by LPS; compounds 1, 2 and 4 significantly decreased the activity of NF-κB in LPS-induced RAW 264.7 cells (all P < 0.05). In conclusion, compounds 1, 2 and 4 have certainly anti-inflammatory effects on LPS-induced RAW 264.7 cell inflammation, and their possible mechanism of action is to inhibit the NF-κB signaling pathway and the transcriptional expression of downstream inflammatory mediators, inhibit the secretion of HMGB1, and relieve the inflammatory response of LPS-induced RAW 264.7 cells.