Accumulating evidence has implicated glutamatergic systems in psychiatric disorders. Abnormalities in glutamatergic systems have consistently been identified in obsessive-compulsive disorder (OCD). Marble-burying behavior has been described in literature as a potentially useful measure for modeling OCD in mice. However, involvement of glutamatergic systems in marble-burying behavior has largely remained unexplored. Here, the effects of an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor potentiator, CX546, and an NR2B subunit-containing N-methyl- d-aspartate (NMDA) receptor antagonist, Ro25-6981, were examined using a marble-burying test. Treatment with highest dose (30.0 mg/kg) of CX546 significantly inhibited the marble-burying behavior. Moreover, treatment with Ro25-6981 also significantly reduced the marble-burying behavior. In contrast, both drugs did not affect locomotor activity in mice. The present results suggest that glutamatergic systems might be related to marble-burying behavior. Furthermore, agents targeting glutamateric systems such as an AMPA receptor potentiator and an NR2B receptor antagonist, may be useful in treating OCD.