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NFL Leaders |
| Rank | Player | Team | G | Rushes | Yds | Yd/G | Avg | TD |
| 1 | M. Jones-Drew | Jac | 16 | 343 | 1606 | 100.4 | 4.68 | 8 |
| 2 | R. Rice | Bal | 16 | 291 | 1364 | 85.3 | 4.69 | 12 |
| 3 | A. Foster | Hou | 13 | 278 | 1224 | 94.2 | 4.40 | 10 |
| 4 | C. Benson | Cin | 15 | 273 | 1067 | 71.1 | 3.91 | 6 |
| 5 | C. Johnson | Ten | 16 | 262 | 1047 | 65.4 | 4.00 | 4 |
| 6 | M. Bush | Oak | 16 | 256 | 977 | 61.1 | 3.82 | 7 |
| 7 | S. Greene | NYJ | 16 | 253 | 1054 | 65.9 | 4.17 | 6 |
| 8 | W. McGahee | Den | 15 | 249 | 1199 | 79.9 | 4.82 | 4 |
| 9 | R. Mendenhall | Pit | 15 | 228 | 928 | 61.9 | 4.07 | 9 |
| 10 | R. Mathews | SD | 14 | 222 | 1091 | 77.9 | 4.91 | 6 |
| 11 | R. Bush | Mia | 15 | 216 | 1086 | 72.4 | 5.03 | 6 |
| 12 | B. Green-Ellis | NE | 16 | 181 | 667 | 41.7 | 3.69 | 11 |
| 13 | B. Tate | Hou | 15 | 175 | 942 | 62.8 | 5.38 | 4 |
| 14 | F. Jackson | Buf | 10 | 170 | 934 | 93.4 | 5.49 | 6 |
| 15 | D. Thomas | Mia | 13 | 165 | 581 | 44.7 | 3.52 | 0 |
| 16 | P. Hillis | Cle | 10 | 161 | 587 | 58.7 | 3.65 | 3 |
| 17 | T. Jones | KC | 16 | 153 | 478 | 29.9 | 3.12 | 0 |
| 18 | J. Battle | KC | 15 | 149 | 597 | 39.8 | 4.01 | 2 |
| 19 | D. Brown | Ind | 16 | 134 | 645 | 40.3 | 4.81 | 5 |
| 20 | T. Tebow | Den | 14 | 122 | 660 | 47.1 | 5.41 | 6 |