Having a quick peek at the source for Log::Log4perl::Appender::File it would appear that it will not be thread-safe due to its lack of file locking. But if you're using the Log::Log4perl::Appender::DBI layer you should be fine as DBI is thread-safe (in theory, at least).

As for a solution, I'd say just override the specific logging methods e.g

sub Log::Log4perl::Appender::File::log {
    my($self, %params) = @_;

    my $fh = $self->{fh};

    flock( $fh => LOCK_EX );
    print $fh $params{message};
    flock( $fh => LOCK_UN );

    if ($self->{autoflush}) {
        my $oldfh = select $self->{fh}; 
        $| = 1; 
        select $oldfh;
    }
}
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Or perhaps create just a wrapper function/method that does the flocking before and after the call to the logging function.