Butyrate has multiple protective effects in inflammation-related intestinal diseases. Previous studies have found that butyrate could inhibit inflammation in rheumatoid arthritis. Inflammation is a pivotal inducement in the degeneration progress of the intervertebral disc. The anti-inflammatory treatment has an apparent curative effect in the symptomatic treatment of spine-related disease. Herein we investigated whether butyrate plays a protective role in degenerated intervertebral disc model. To mimic the lumbar disc local inflammatory environment, human primary nucleus pulposus cells were cultured with interleukin-1β (IL-1β, 10 ng/ml) to build a nucleus pulposus cell inflammation model. Butyrate was added to the cell culture medium to test the effect of butyrate on disc inflammation. Furthermore, a cultured nucleus pulposus tissue model was treated with butyrate (1 mM) to simulate the local treatment of intervertebral disc disease. Herein, we found that butyrate could downregulate the production of the inflammatory mediator caused by IL-1β stimulation in the cell culture model. Additionally, butyrate inhibits the secretion of pro-inflammatory cytokines or graded enzymes in disc tissues from lumbar disc herniation patients. Furthermore, the anti-inflammatory function of butyrate in lumbar disc degenerated model may be caused by inhibiting the activation of the nuclear factor kappa B (NF-κB) signal pathway. This study presents butyrate as a candidate therapeutic method to treat lumbar disc degenerative disease.