An activation of Kupffer cells (hepatic resident macrophages) and hepatic stellate cells (HSCs) plays an important role in lipopolysaccharide (LPS)‐induced liver injury. It is known that the upregulated production of ET‐1 by Kupffer cells in response to LPS stress activates HSCs and induces subsequent pathophysiological change in the liver. Recently, it has been reported that some amino acids exhibit anti‐inflammatory effects. In a preliminary experiment, using 20 amino acids, we investigated the effect of amino acid administration on ET‐1 production in the mouse macrophage cell lines (RAW 264.7). Among the amino acids, L‐cysteine, L‐glutamine, L‐leucine, L‐alanine, and Glycine suppressed LPS‐induced ET‐1 production in a dose‐dependent fashion. The effect was strongest by an administration of L‐cysteine. L‐cysteine also suppressed a ET‐1‐induced contraction of collagen gel lattices cultured with HSCs. Moreover, an increased [Ca2+]i in response to ET‐1 administration in HSCs measured with the fluorescent dye fura‐2 was strongly attenuated with the presence of L‐cysteine in a culture medium. In an in vivo experiment, Wister rats were pre‐treated with L‐cysteine or saline and received intravenous injection of LPS. Increased levels of liver function tests following LPS was attenuated by L‐cysteine treatment. These results indicated that L‐cysteine may lead to a beneficial effect in LPS‐induced liver injury.