There's a great synopsis of Kerouac's follow up to On the Road here. I'm a bit reticent to talk about this book today, but suffice it to say that I love Kerouac's writing, and especially this book. All of Kerouac's books are highly autobiograhpical and what strikes me most about his work is its honesty and sincerity; Kerouac is not afraid to wear his feelings on his sleeve when he writes, even when it makes him look silly or stupid.
Another appealing aspect of DB is the desire for freedom that the protagonist Ray Smith (none other than Kerouac himself) aspires to. It's simultaneously refreshing and frustrating to watch Ray Smith stumble through life, seeking out the ultimate expression of freedom from samsara, or life's suffering. Every time I read the opening chapter of DB, I have an irresistable desire to hop on a grayhound and go west.
All that being said, I think most modern readers might find Kerouac's work to be a bit naive. Times have changes enormously since the Beats first set the scene, and the wild and crazy antics of Kerouac and his friends seem a bit mundane by modern comparisons. At the same time, it is just this sense of innocence that makes the work appealing. What I would give for a summer on Desolation Peak, or of hiking in the Marin foothills, just bumming around without any real need to be productive or chained to a job. :-)