We report systematic variations in the CO(2-1)/CO(1-0) line ratio (R) in M51. The ratio shows clear evidence for the evolution of molecular gas from the upstream interarm regions, passage into the spiral arms and back into the downstream interarm regions. In the interarm regions, R is typically low <0.7 (and often 0.4-0.6); this is similar to the ratios observed in Galactic giant molecular clouds (GMCs) with low far-IR luminosities. However, the ratio rises to >0.7 (often 0.8-1.0) in the spiral arms, particularly at their leading (downstream) edge. R is also high, 0.8-1.0, in the central region. An LVG calculation provides insight into the changes in the gas physical conditions between the arm and interarm regions: cold and low density gas (~10K, ~300cm-3) is required for the interarm GMCs, but this gas must become warmer and/or denser in the more active star forming spiral arms. R is higher in areas of high 24micron brightness (an approximate tracer of star formation rate surface density) and high CO(1-0) integrated intensity (a well-calibrated tracer of total molecular gas surface density). The systematic enhancement of the CO(2-1) line relative to CO(1-0) in luminous star forming regions suggests that some caution is needed when using CO(2-1) as a tracer of bulk molecular gas mass.