Abstract: In order to analyze plutonium isotope ratios precisely at picogram levels by multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS), the various parameters of instrument were optimized. The interference caused by uranium, thorium, lead and other metal ions were studied. The mass bias and the inter-detector bias can be obtained by using the reference material of uranium. The results that the accuracy of 240Pu/239Pu is less than 0.5% at 50 pg·g－1 level when this method is utilized.