In this work we report that the biodistribution and excretion of carbon nanohorns (CNHs) in mice are dependent on their size and functionalization. Small-sized CNHs (30-50 nm; S-CNHs) and large-sized CNHs (80-100 nm; L-CNHs) were chemically functionalized and radiolabeled with [111In]-diethylenetriaminepentaacetic acid (DTPA) and intravenously injected into mice. Their tissue distribution profiles at different time points were determined by single photon emission computed tomography (SPECT/CT). The results showed that the S-CNHs circulated longer in blood, while the L-CNHs accumulated faster in major organs like the liver and spleen. Small amount of S-CNHs- and L-CNHs were excreted in urine within the first few hours post-injection, followed by excretion of smaller quantities within the next 48h in both urine and feces. The kinetics of excretion for S-CNHs were more rapid than for L-CNHs. Both nanohorn material accumulated mainly in the liver and spleen, however, S-CNH accumulation in spleen was more prominent than in the liver.