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<P><B>Abstract</B></P><P>The chronic toxicity test has been conducted for twenty-eight days to characterize the hepatic expression levels of eight stress-related genes after exposing Medaka to two doses of silver nitrate or a silver nanoparticle (Ag-NP) using real time RT-PCR analysis. This extends our previously published work to include three additional biomarkers and three later time points. In comparing with the control, the significant induction of MT and GST genes in livers of the fish exposed to 1μg/l Ag-NPs was observed at various time points during the test period. The <I>Orla C3-1</I> (Medaka) gene was slightly induced only with 1μg/l Ag-NPs at 7-day exposure while the suppression of p53 and HSP70 was recorded in all exposures at the end of the test. The gene encoding transferrin was repressed at day 21 by both silver types and at every exposure dosage. These results revealed that the Ag-NPs increase metal detoxification, oxidative and inflammatory stress, and finally stimulate immune responses in Medaka. The conspicuous induction of choriogenin L and vitellogenin 1 in male fish exposed to Ag-NPs, especially at 7- and 21-day, compared with the exposures of AgNO<SUB>3</SUB> or control was the first attempt to examine estrogenic effects of Ag-NPs.</P> <P><B>Highlights</B></P><P>► Male Medaka were exposed to two doses of AgNO<SUB>3</SUB> or Ag-NPs for 28 days. ► Hepatic expression level of eight stress-related genes was characterized. ► Ag-NPs increase metal detoxification, oxidative and inflammatory stresses. ► Our study is the first attempt to examine estrogenic effects of Ag-NPs.</P>