After upgrading to Zabbix 2.2.3 my proxy queue just exploded. There is practically no load on the machines at the time of writing.
Restarting the proxies did not help, neither did rebuilding the local proxy db (running sqlite3 proxies with the db files in tmpfs).
I've even rebooted the server and proxies to no avail.
I've moved all of my hosts over to my server, the queue is empty now.
Please also see https://www.zabbix.com/forum/showthread.php?p=148298#post148298