This study was aimed to evaluate antioxidant activities of a methanol extract from the polar microalgae Fragilariopsis pseudonana (FP) and to investigate the protective effect for gap junctional intercellular communication (GJIC) in WB-F344 normal rat liver epithelial cells. The results indicated that the methanol extract of FP (FPM) scavenged ABTS free radicals and inhibited copper-induced low density lipoprotein oxidation in a dose-dependent manner. Exposing HepG2 cells to $FeSO_4$ increased intracellular reactive oxygen species formation and lipid peroxides, which was significantly reduced by treatment with FPM. Furthermore, FPM increased the activities of superoxide dismutase and glutathione peroxidase in cells. FPM recovered the hydrogen peroxide ($H_2O_2$)-induced inhibition of GJIC and attenuated the phosphorylation of connexin 43 (Cx43) and extracellular signal-regulated kinase1/2 (ERK1/2). Taken together, these results demonstrated that FPM has antioxidant activity and protects against $H_2O_2$-induced inhibition of GJIC by blocking phosphorylation of Cx43 via activation of ERK1/2.