Most studies have used in vitro systems to test inflammatory responses of nanoparticles; these may not reflect the real biological response of body organs. In fact, certain nanoparticles have provoked opposite effects under in vitro and in vivo conditions. Current understanding of the biocompatibility of gold nanoparticles is controversial. We studied the acute (1 day) and sub-chronic (5 days) effects of gold nanoparticles (10 and 50 nm in diameter) on expression of interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α) in rat liver. Real-time PCR analysis showed that gold nanoparticles of both sizes significantly increased cytokine gene expression on day 1; this had subsided by day 5. The 50-nm gold nanoparticle produced more severe inflammation than the smaller gold nanoparticle. These findings indicate a possible biocompatibility of medium-sized gold nanoparticles, as they caused only a transient increase in proinflammatory cytokines, followed by normalization during sub-chronic repeated exposure.