The present study investigated the cellular mechanism underlying the effect of ligustrazine on the ion transport in rat distal colon using the short-circuit current (I(SC)) technique. In freshly isolated colonic strips, basolateral addition of ligustrazine stimulated a rise in I(SC), which was resistant to basolateral application of neuronal sodium channel blocker tetrodotoxin (TTX), but inhibited by 55.2% by basolateral pretreatment with prostaglandin inhibitor indomethacin. The ligustrazine-induced I(SC) increase was inhibited by apical application of Cl(-) channel blockers diphenylamine-2,2'-dicarboxylic acid (DPC) and glibenclamide. Basolaterally administered bumetanide, an inhibitor of Na(+)-K(+)-2 Cl(-) cotransporter, inhibited ligustrazine-evoked current increases by 85.2% and basolateral exposure to Ba(2+), a non-specific potassium channels blocker, and blocked the current by more than 90%, indicating that basolateral Na(+)-K(+)-2 Cl(-) cotransporter and K(+) channels played an important role in the effect of ligustrazine. The results suggested that ligustrazine could stimulate rat distal colon (-) secretion that is mediated by basolateral Na(+)-K(+)-2 Cl(-) cotransporter and K(+) channel.