Propofol (2,6-diisopropylphenol) is one of the most commonly used intravenous anesthetics. Anesthetics can regulate the inflammatory process; however, the mechanism remains to be fully elucidated. The present study aimed to investigate whether and how propofol affects the inflammatory reaction in human umbilical vein endothelial cells (HUVECs). The expression levels of Toll‑like receptor 4 (TLR4) and cluster of differentiation 14 (CD14) were determined in HUVECs treated with propofol and lipopolysaccharide (LPS) using western blot and reverse transcription‑quantitative polymerase chain reaction analyses. In addition, whether propofol regulated the expression of TLR4 though microRNA (miR)‑21 was examined. The results showed that LPS promoted the expression levels of TLR4, CD14 and tumor necrosis factor α (TNFα), and suppressed the expression of miR‑21 in HUVECs. Propofol suppressed the expression levels of TLR4, CD14 and TNFα, and upregulated the expression of miR‑21 in a concentration‑dependent manner. miR‑21 downregulated the expression of TLR4 at the mRNA and protein levels, whereas the miR‑21 mimic reversed the effect of LPS on the expression of TLR4. In addition, the miR‑21 inhibitor inhibited the downregulatory effect of propofol on the expression of TLR4. TargetScan analysis showed that TLR4 was included in the list of targets of miR‑21. Fluorescent reporter assays showed that the miR‑21 mimic and propofol treatment reduced the fluorescence intensity in cells transfected with a reporter vector containing the wild‑type TLR4 3'‑untranslated region. Taken together, the results of the present study demonstrated that propofol regulated the expression of TLR4 in HUVECs through miR‑21.