Titanium dioxide (TiO(2)) is one kind of widely used nanoparticle, which was used as a solid-phase extraction to preconcentrated and measured of lead (Pb) in river water and seawater. However the interaction of nanoparticle TiO(2) and Pb was unknown. The aim of this study is to investigate the potential acute toxicity of the interaction between nanoparticle TiO(2) (50 and 120nm) and lead acetate (PbAC) in adult mice. The animals were randomly divided into six groups: a control group and five treatment groups (TiO(2)-50, TiO(2)-120, PbAC, TiO(2)-50+PbAC and TiO(2)-120+PbAC groups). Suspensions of TiO(2) (5g/kg body weight), PbAC (500mg/kg body weigh) and TiO(2) (5g/kg body weight)+PbAC (500mg/kg body weigh) were administrated to mice via oral gavage, respectively. Seven days later, the animals were sacrificed after being anesthetized by ether. There were no significant changes of the body weight coefficients of liver, kidney and brain. However, the results of liver function and nephrotoxicity examination revealed that there were serious damages to liver and kidney between the group treated with the mix suspension and the one with TiO(2). After the mix suspension treatment, ROS levels were significantly increased in liver but not in kidney, cortex and hippocampus. There were no increase of MDA levels in these tissues, and no activity reductions of SOD and GSH-Px in liver and kidney but in the cortex and hippocampus. Therefore, though our results have not suggested that TiO(2) particle and PbAC have a synergistic acute toxicity in mice after oral administration, PbAC may increase the acute toxicity of TiO(2) nanoparticle in some degree. The potential toxic mechanism maybe related with oxidative damages.