Diphenyl diselenide ([PhSe]2)is an organoselenium compound that has interesting pharmacological properties, including antioxidant, glutathione peroxidase-mimetic, and neuroprotective effects. The objective of the present study was to investigate the possible modulatory effect of (PhSe)2 in 17th-generation Carioca high-and low-conditioned freezing (CHF and CLF) rats, an animal model of generalized anxiety disorders. (PhSe)2 was administered at three doses (10, 50, and 100mg/kg) in CHF and CLF rats, and their anxiety-like profiles (conditioned freezing patterns) were measured before and 30min after treatment. A significant difference was found in freezing scores between CHF and CLF animals before treatment (t70=12.50, p<0.001). Treatment with (PhSe)2 at 10 and 50mg/kg decreased freezing in CHF rats but significantly increased freezing at 100mg/kg. (PhSe)2 increased freezing in CLF animals at 50 and 100mg/kg (p<0.01). These results indicate that (PhSe)2 exerts both anxiolytic- and anxiogenic-like effects in bi-directional rat lines. Distinct genetic profiles of the CHF and CLF lines may influence biochemical functions and lead to differential responses to aversive situations and various drugs like (PhSe)2.